Point-of-care diagnostic cartridge having a lateral flow assaying apparatus

ABSTRACT

A specimen processing cartridge includes a reservoir having a fluid inlet, an elastic diaphragm, and a fluid outlet. The reservoir is operable to receive a volume of liquid from the fluid inlet, and the fluid outlet is positioned along a fluid flow path between the reservoir and a downstream reservoir. The cartridge includes a dissolvable membrane that occludes flow through the fluid outlet when the dissolvable membrane is in a first, undissolved state, and that permits flow from the reservoir to the downstream reservoir when in a second, dissolved state. The elastic diaphragm is operable to pressurize the reservoir upon receiving the volume of liquid when the dissolvable membrane is in the first, undissolved state, and is operable to contract and propel at least a portion of the volume of liquid from the reservoir to the downstream reservoir when the dissolvable membrane is in the second, dissolved state.

TECHNICAL FIELD

The present disclosure relates generally to the field of medicaldiagnostics and more particularly to in vitro medical diagnostic devicesincluding point-of-care in vitro medical diagnostic devices.

BACKGROUND OF THE INVENTION

There is a recognized and compelling need for the rapid and accuratediagnosis of common infectious diseases in an out-patient setting. Thisneed results from a rapidly emerging trend toward what is sometimesreferred to as “patient centric care” in which convenience—along withbetter health outcomes and low cost—becomes a key market driver.

The field of in vitro diagnostics is well established, with manymanufacturers and a wide spectrum of products and technologies. Thetesting for infectious pathogens in human patient specimens is largelyconfined to centralized laboratory testing in Clinical LaboratoryImprovement Amendment (CLIA) rated medium-complexity or high-complexityfacilities. Commonplace techniques used in such laboratories includetraditional culturing of specimens, immunological assaying usingEnzyme-Linked Immunosorbent Assay (ELISA), nucleic acid testing (such aspolymerase chain reaction, PCR), and other methods.

Many different types of devices can be used to complete diagnosticprocesses in centralized laboratories. It has been historicallydifficult, however, to complete such diagnostic processes entirely, oralmost-entirely in an outpatient setting where equipment and materialsthat are common-place in a laboratory may not be readily available orare suitable for use. As a result, relatively few devices are readilyavailable that are able to complete diagnostic processes in the field(meaning outside of a laboratory environment) without access to theresources of a laboratory.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic, perspective view of an illustrative embodiment ofa specimen delivery cartridge;

FIG. 2 is a schematic, perspective view of the specimen deliverycartridge of FIG. 1 in an open configuration;

FIG. 3 is a bottom, section view of the specimen delivery cartridge ofFIG. 1, as indicated by the lines 3-3 shown in FIG. 5;

FIG. 4 is a side, section view of the specimen delivery cartridge ofFIG. 1, taken along the arrows 4-4 shown in FIG. 5;

FIG. 5 is a side, section view of the specimen delivery cartridge ofFIG. 1, taken along the arrows 5-5 shown in FIGS. 3 and 4;

FIG. 6 is a detail, section view of a portion of the specimen deliverycartridge, as indicated in FIG. 5;

FIG. 7 is an exploded, perspective view showing an assembly of aspecimen delivery cartridge with a mating adaptor and a computingdevice;

FIG. 8 is a schematic, side-section view of a capillary plate apparatus,or “lateral flow assaying apparatus”;

FIG. 9 is a schematic, perspective view of the capillary plate apparatusof FIG. 8; and

FIG. 10 is a detail, side section view of a viewing area of thecapillary plate apparatus of FIG. 8.

SUMMARY

In accordance with an illustrative embodiment, a specimen processingcartridge includes a reservoir having a fluid inlet, an elasticdiaphragm, and a fluid outlet. The reservoir is operable to receive avolume of liquid from the fluid inlet, and the fluid outlet ispositioned along a fluid flow path between the reservoir and adownstream reservoir. The cartridge includes a dissolvable membrane thatoccludes the fluid outlet when the dissolvable membrane is in a first,undissolved state, and that permits flow from the reservoir to thedownstream reservoir when in a second, dissolved state. The elasticdiaphragm is operable to pressurize the reservoir upon receiving thevolume of liquid when the dissolvable membrane is in the first,undissolved state. The elastic diaphragm is operable to contract andpropel at least a portion of the volume of liquid from the reservoir tothe downstream reservoir when the dissolvable membrane is in the second,dissolved state.

In accordance with another illustrative embodiment, a method forimplementing a diagnostic process includes delivering a volume of liquidto a reservoir of a diagnostic device via a fluid inlet. The diagnosticdevice includes the reservoir, an elastic diaphragm positioned within aboundary of the reservoir, a fluid outlet port positioned along a fluidflow path from the reservoir to a downstream reservoir, and adissolvable membrane that occludes the fluid flow path when thedissolvable membrane is in a first, undissolved state, and that permitsflow from the reservoir to the downstream reservoir when in a second,dissolved state. The method further includes applying a positivepressure to the reservoir, thereby causing expansion of the elasticdiaphragm when the dissolvable membrane is in the first, undissolvedstate, and exposing the dissolvable membrane to the volume of liquid.The dissolvable membrane dissolves after a predetermined amount of timelapses following exposure to the volume of liquid, and dissolution ofthe dissolvable membrane permits the elastic diaphragm to contract andpropel at least a portion of the volume of liquid from the reservoir tothe downstream reservoir.

DETAILED DESCRIPTION

Conventional models for infectious disease diagnosis rely heavily oncentralized laboratory testing (e.g. culture), which can often take twoto four days to provide a reliable result. A consequence of conventionalmodels is that patients are not necessarily properly diagnosed on theirfirst visit; nor are they given the correct drug prescription. This canresult in money wasted on either incorrect or unnecessary prescriptions,inconvenience to patients owing to repeat visits, and even the potentialfor otherwise treatable illnesses to progress to more serious conditionsrequiring expensive hospital stays. In diagnosing a patient, it iscommon for a physician to ask whether an illness is the consequence of abacterial or a viral pathogen. In seeking to answer the foregoingquestion, incomplete or inaccurate diagnoses can result in theover-prescription of antibiotics, which is a cost burden to thehealthcare system. Perhaps more importantly, incorrect diagnoses maycontribute to the increasing frequency of antibiotic resistant strainsin the community, which is a national health concern.

Seeking to improve upon the conventional model, some rapid diagnostictests (RDTs) have been brought to market for use in an out-patientsetting. Many of these RDTs, however, are simple “rule-in/rule-out”tests which do not necessarily inform clinical decision-making. Manysuch RDTs also suffer from poor sensitivity and specificity, making thevalidity and clinical utility of their results unreliable. The presentdisclosure relates to a system that is able to provide accuratediagnoses during a patient visit and with a high degree of accuracy.

The present disclosure provides for a point-of-care diagnostic devicefor use in determining the presence of a target infectious disease in abiological specimen. The illustrative embodiments provide a lowcomplexity and low-cost solution while providing a mechanism forimproving health outcomes as compared to the state of the art. Further,to leverage the ubiquity of smartphones and other computing devices incommon use globally, an illustrative specimen processing cartridge mayfacilitate the use of a computing device, such as a smartphone, to carryout certain processes in testing for one or more pathogens.

More particularly, the present disclosure relates to a specimenprocessing cartridge that may be deployed in any useful context, but isdescribed in the present disclosure in the context of processing abiological specimen. In some illustrative embodiments, the cartridgeprovides a flow channel that may be populated with reagents or coupledto one or more fluid inlets to receive reagents from differentreservoirs and facilitate wicking or capillary flow across a viewingarea. In an exemplary embodiment, different reagents may be introducedto a viewing area using different methods. Various liquids, which mayinclude the reagents, flow across a main channel of flow through theviewing area at different times to facilitate execution of a diagnostictest.

The differing reagents may be introduced at different times to allow forsufficient time for the occurrence of reaction with embedded reagents ona substrate or capillary plate apparatus positioned within the mainchannel. As referenced herein, a capillary plate apparatus is intendedto describe a structure comprising offset surfaces that are separated bya relatively short distance to form a channel between the surfaces thatfacilitates capillary flow. The offset surfaces may be substantiallyparallel or may be out of parallel and merely sufficiently close to oneanother to facilitate capillary flow across the channel.Correspondingly, the referenced plates should also be understood to bemembers having opposing surfaces that may or may not be planar, as theremay be variable configurations (e.g., contoured surfaces or surfaceshaving a variable offset) in which the plates facilitate capillary flowbut are not necessarily planar or parallel to each other. The channelmay be open at the sides or enclosed. For example, side seals or acontiguous portion of material may be present at the sides of thechannel to provide an enclosure.

In embodiments including a capillary plate apparatus, the apparatus maybe formed from opposing (possibly parallel) plates that form a capillarychannel and are optimized to facilitate viewing of one or moreidentified viewing areas, or detection zones of the capillary plateapparatus. As referenced herein, a detection zone is a portion of theflow channel that is viewable by a user or computing device of a user toperform at least a portion of an assaying process. The detection zonemay include one or more detection locus (or loci), as described in moredetail below.

The present disclosure also relates to a specimen processing cartridgehaving functionality that provides for the timing and metering of thedelivery of liquids to a testing area. An exemplary cartridge mayinclude a plurality of reservoirs for storing and processing liquids asthey flow toward the testing area. For example, the cartridge mayinclude a downstream reservoir that holds a sample collection liquidafter the sample collection liquid has been interacted with a sampleuntil the cartridge is placed in a specific wicking orientation.Placement of the cartridge in the wicking orientation may result inliquid in the downstream reservoir contacting a wicking substrate thatcarries the liquid along a fluid flow path across the testing area.

The specimen processing cartridge may also store one or more liquidsthat may be mixed together in an intermediate reservoir. Placement ofsuch a processing cartridge in the wicking orientation may result in asecondary liquid in the intermediate reservoir contacting a dissolvablemembrane that is configured to dissolve after a predetermined amount oftime based on the composition and thickness of the membrane. Thepredetermined amount of time may correspond to the amount of time ittakes for the sample collection liquid to evacuate the downstreamreservoir. Expiration of the predetermined amount of time may allowadditional time for the sample collection liquid to interact withreagents or other diagnostic materials at the testing area beforeadditional flow is permitted from the intermediate reservoir to thedownstream reservoir. This allows for the timed sequencing of flowsacross the viewing area.

The dissolvable membrane may rupture after the expiration of thepredetermined amount of time, thereby permitting the secondary liquid toflow into the downstream reservoir, and ultimately to the testing areavia the wicking substrate. Flow from the intermediate reservoir to thedownstream reservoir may be aided by an expandable diaphragm, whichexpands when the secondary liquid is forced into the intermediatereservoir, which is already occupied by air or another suitable gas, andcontracts to propel the secondary liquid from the intermediate reservoirwhen the dissolvable membrane ruptures. By expanding in the describedmanner, the expandable diaphragm allows for the displacement of air inthe intermediate reservoir (into the increased volume provided byexpansion of the diaphragm) when the secondary fluid is forced into theintermediate reservoir.

Referring now to the figures, FIG. 1 shows an illustrative embodiment ofa specimen processing cartridge 100. The processing cartridge 100 mayoperate to further process a specimen that has already been subject toprior processing steps or to process a specimen that has recently beengathered from a patient. To that end, this disclosure is not intended tobe limited in its application to a specimen processing cartridge 100whose processing capability is limited to what is described. Rather, thedisclosure is intended to illustrate the operative capabilities of thedescribed specimen delivery cartridge, with an understanding thatdiscrete portions of the illustrative specimen processing cartridge 100may have independent utility if deployed in alternative apparatus. Forexample, a capillary plate apparatus may be deployed in an alternativedevice that uses mechanisms and features other than those describedherein to supply liquids to the fluid inlet of any type of downstreamapparatus.

In the specimen processing cartridge 100 of FIGS. 1-7. The specimendelivery cartridge 100 includes a cartridge body 106, which may bealternatively referred to as a first portion, and a lid 108, which maybe alternatively referred to as a second portion. The lid 108 is coupledto the body 106 at a hinge 116. The lid 108 closes toward the body 106to enclose a shaft port 110 for receiving a specimen collection device,such as a swab. The specimen collection device may be used to deliver abiological specimen or sample taken from a patient, such as saliva, atissue sample, or a sample of bodily fluids.

FIG. 2 shows the specimen delivery cartridge 100 with the lid 108 open.The specimen delivery cartridge 100 may be understood as including ahousing 105 that is made up of the body 106 and lid 108. The housing 105has an open state and a closed state, and may be closed by moving thelid 108 toward the body 106 to transition from the open state to theclosed state. The housing 105 includes an intermediate member 109 havinga first cavity 133 that mates with a second cavity 135 formed in the lid108 to form a specimen receiving chamber 134.

The specimen delivery cartridge 100 is shown as including a firstactuation port 102 and second actuation port 104. The actuation portsmay be operable to receive actuation posts or prongs from a matingadapter or similar device to actuate an internal fluid flow process, asdescribed in more detail below. The specimen delivery cartridge 100 isalso shown as including an actuator 114 which may form a portion of afirst reservoir 120, which may be a “collection fluid reservoir” suchthat the actuator 114 may be depressed by a user to initiate a fluidflow process (as also described in more detail below). To that end, theactuator 114 is operable to move fluid a sample collection liquid withinthe specimen delivery cartridge 100 when the housing 105 is in theclosed state and the actuator 114 is depressed or otherwise actuated. Inthe illustrated embodiment, the actuator 114 is a bulb-type actuator. Inother embodiments, a piston-cylinder, electronic actuator, or othersuitable type of actuator may be used.

The sample collection liquid may be stored within the first reservoir120 prior to actuation and held in place by a destructible seal thatprevents the sample collection liquid from exiting the first reservoir120 through a port that is fluidly coupled to the specimen receivingchamber 134 while the seal is intact. Actuation of the actuator 114 mayresult in destruction (e.g., by pressurization or otherwise) of thedestructible seal to allow for the communication of sample collectionliquid from the first reservoir 120 to the specimen receiving chamber134. A locking mechanism to hold the actuator 114 in the engagedposition, or a check valve may be included at the referenced port sothat once the actuator 114 has been engaged and sample collection liquidevacuated from the first reservoir 120, the sample collection liquid maynot return to the first reservoir 120.

In some embodiments, the first reservoir 120 may be a blister pack. Inothers, the first reservoir 120 may be a cylinder, a liquid-filled bulb,or other similar container that may be evacuated when a hydraulic forceis applied upon actuation by the actuator 114. The first reservoir 120may be pre-filled with a sample collection liquid, which is a fluid thatis selected to strip sample from a specimen collection device and carrythe sample in suspended, diluted, or dissolved form through the fluidflow paths described below. The sample collection liquid may include areagent such as a lysing agent to react with the sample, an elutionbuffer, an anti-coagulant or a solvent. The actuator 114 is operable togenerate a hydraulic force to propel the sample preparation fluid fromthe first reservoir, through a tube, and through the specimen receivingchamber 134, and ultimately to a third reservoir 130, which may also bereferred to as a “downstream reservoir.”

The specimen receiving chamber 134 may be sized and configured toreceive a specimen collection device (e.g., a swab) and facilitateextraction of the sample from the specimen collection device. In someembodiments, the specimen receiving chamber 134 includes features thatroil the sample collection liquid passing through the specimen receivingchamber 134. As referenced herein, “roiling” refers to the manipulationof a fluid in a manner that induces turbulence or increased fluid shearforces to facilitate extraction of a specimen for analysis from aspecimen collection device. For example, the specimen receiving chamber134 may include helical or spiral features that induce vortex flow orspiral-like flow patterns, such as grooves. Such features may inducehigh fluid shear forces in the sample preparation fluid, increaseturbulent energy and result in a higher Reynolds number. The foregoingcharacteristics may be understood to enhance the ability to extract aspecimen for analysis from a specimen collection device placed in thechamber. In some embodiments, the roiling features may be spiralizedgrooves that engage or nearly engage the shaft of the specimencollection device to force the sample preparation fluid to follow ahelical flow path through the sample collection portion of the specimencollection device as it is propelled through the specimen receivingchamber 134. For clarity, it is noted that in the context the samplepreparation described in this disclosure, “extraction” does not relateto pulling DNA from a cell. Instead, “extraction” refers generally tothe ability to recover organisms, molecules or other particles ofinterest off from a collection device and deliver those particles to asubsequent stage for further analysis.

The shaft portion of a swab or other suitable sample collection devicemay be deemed a nuisance once the sample is acquired and placed withinthe specimen processing cartridge 100. To facilitate removal of theportion of the shaft that extends beyond the housing 105 of the specimenprocessing cartridge 100, a swab may have a pre-scored shaft tofacilitate breaking off the protruding portion of the swab shaft.Alternatively, the specimen processing cartridge 100 may include a swabcutter 112 to neatly trim away excess swab shaft material. Moreover, aswab shaft seal may be included where the shaft is inserted into thehousing 105 of the specimen processing cartridge 100 and the adjoiningexternal boundaries of specimen receiving chamber 134 may include asimilar gasket or other suitable seal to form a sealed liquid flow paththrough the specimen receiving chamber 134.

FIG. 3 is a section view of the specimen delivery cartridge 100 of FIG.1 and illustrates operational features of the specimen deliverycartridge 100. This illustration also shows a first actuation port 102and second actuation port 104 which, respectively, are coupled to orinclude, and therefore correspond with, a first storage reservoir 122and a second storage reservoir 124. Here, it is noted that while onlytwo actuation ports and two associated fluid sources are referenced, anysuitable number of actuation ports and fluid sources (e.g., n actuationports and n storage reservoirs may instead be included). Each of thefirst storage reservoir 122 and second storage reservoir 124 isrespectively coupled to a first conduit 146 and second conduit 148 whichoperates as a fluid coupling (or a respective first fluid inlet andsecond fluid inlet) to a intermediate reservoir, which may also bereferred to as an intermediate reservoir. Each of the first storagereservoir 122 and second storage reservoir 124 may be actuated by anactuation post or similar mechanism that applies a compressive force tothe applicable fluid source, thereby motivating a volume of liquidstored within the fluid source(s) to flow through the applicable conduitand into the intermediate reservoir 126.

The intermediate reservoir 126 is a cavity enclosed at a top surface(when oriented as depicted in FIGS. 4 and 5) by an expandable, elasticdiaphragm 128 positioned within a boundary or wall of the intermediatereservoir 126, and at a fluid outlet (intermediate reservoir outlet 136)by a dissolvable membrane 150 or similar frangible device. Thedissolvable membrane 150 may be made from a polyvinyl alcohol, or othersuitable membrane material. The expandable, elastic diaphragm 128 isoperable to expand when one or more pressurized fluids are delivered tothe intermediate reservoir 126. In some instances, it may be desirableto allow for mixing of fluids before the fluids are permitted to drainfrom the intermediate reservoir 126 through the intermediate reservoiroutlet 136 and into the downstream reservoir, which may also be referredto as a downstream reservoir 130. Further, in some embodiments it may bedesirable to include a baffle 152 between the fluid inlets (firstconduit 146 and second conduit 148) of the intermediate reservoir 126and the dissolvable membrane 150 to minimize the occurrence of prematureexposure of the dissolvable membrane 150 to liquids transported into theintermediate reservoir 126 from the fluid inlets.

The downstream reservoir 130 is also fluidly coupled to the specimenreceiving chamber 134 by a specimen delivery conduit 132 that is coupledto a specimen inlet 131. The specimen delivery conduit 132 is operableto deliver sample collection liquid that includes the specimen afterextraction from a swab or similar specimen collection device to thedownstream reservoir 130. The downstream reservoir 130 has a portion ofa wicking pad 138 disposed therein that is operable to act as a wickingpath from the downstream reservoir 130 across a viewing area 140 towarda fluid sink 144. The viewing area 140 may be a window, lens, or similarviewing feature that allows for visual inspection of the viewing portion142 of the wicking pad 138. The fluid sink 144 may be a cellulose pad,sponge or other absorbent feature that is operable to provide motivationfor fluid to wick from the downstream reservoir 130 to the fluid sink144. In other embodiments, the fluid sink 144 may be replaced by a fluidoutlet to a reservoir that collects a processed liquid for subsequentprocessing.

In the embodiments shown in the referenced figures, the wicking pad 138is operable to transport a first liquid, which may be the samplecollection liquid received from the specimen receiving chamber 134across the viewing area 140 at a first time, and a second liquid, whichmay be a volume of liquid received from the intermediate reservoir 126across the viewing portion 140 at a second time. The wicking pad 138 maybe a cellulose membrane, a glass fiber substrate, or a similar substratematerial that facilitates wicking of fluid from the downstream reservoir130 to the fluid sink 144. More particularly, the wicking pad 138 may beformed from a microfluidic substrate selected from the group consistingof a glass fiber, cellulose paper, nitrocellulose membrane, or acombination thereof.

In some embodiments, a capillary plate apparatus 209, which mayalternatively be referred to as a “lateral flow assaying apparatus” maysupplant a portion of the wicking pad 138 that passes through theviewing area 140. An example of such a capillary plate apparatus 209 isdescribed with regard to FIGS. 8-10. In embodiments in which thecapillary plate apparatus 209 forms a part of the fluid flow path thatpasses through the viewing area 140, the capillary plate apparatus 209extends from a first end 220 to a second end 222 of a fluid flow path.The second end 222 of the flow path includes or is coupled to the fluidsink 144, either directly or via an intermediate absorbent pad orwicking material. Similar to embodiments in which a wicking pad 138extends across the viewing area 140, the fluid sink in such embodimentsmay be a sponge or similar material that operates as a sink andfacilitates the conduction of liquids from the first end 220 to thesecond end 222 (across the viewing area 140). Between the first end 220and second end 222, the capillary plate apparatus 209 passes across thereferenced viewing area 140, which may also be referred to as a“detection zone.” The detection zone may be aligned with an inspectionwindow or similar feature of the specimen processing cartridge 100(e.g., viewing portion 142) to allow viewing and analysis of the sampleduring operation.

In the embodiment shown in FIG. 8, the capillary plate apparatus 209includes or is coupled to an inlet substrate 211 (analogous to thewicking pad 138 described previously) that is sandwiched between a firstplate 215 and a second plate 213 (or other inlet to a capillary flowchannel). The first plate 215 and second plate 213 may be formed from ahydrophilic polymer, a glass, sapphire, or any other suitable materialor a combination thereof. In some embodiments, one or both of the firstplate 215 and the second plate 213 may have one or more coatings thatenhance capillary action and/or viewability. The first plate 215includes a viewing surface 233 and an opposing inner surface 235. Thesecond plate 213 includes an outer surface 237 and a second innersurface 239, which may also be referred to as a channel-facing surface.A void 217, which operates as a capillary flow path or “capillarychannel,” is bounded by (optional) lateral seals at each side of thecapillary plate apparatus (see first edge 223 and second edge 225 ofFIG. 9), the channel-facing inner surface 235 of the first plate 215,and the channel-facing second inner surface 239 of the second plate 213.At a second end 222, an outlet substrate 219 acts as an interfacebetween the capillary flow path and an absorbent pad 221 that acts as afluid sink, as described above). A complementary, perspective view isshown in FIG. 9, which further illustrates that a first edge 223 and asecond edge 225 of the capillary plate apparatus 209 may be sealed toenclose the capillary flow path. FIG. 9 further illustrates that thecapillary plate apparatus 209 may include a detection zone 204, whichmay correspond to the detection zone or viewing portion 142 describedpreviously.

In alternative embodiments, the capillary flow channel may be formedwithout the use of plates and may be formed using an alternativestructure. In such embodiments, the channel may be formed from, forexample, a relatively flattened ellipsoid structure or similarstructure. In such embodiments, the “first plate” should be understoodto be the portion of the structure that bounds the channel on the sideof the structure that faces the viewing area or viewer. Correspondingly,the “second plate” should be understood to be the portion of thestructure that bounds the opposing side of the channel.

A detail view of a representative detection zone 304 is described withregard to FIG. 10. Within the detection zone 304, a lens array may beformed on or in the viewing surface 233, which is proximate to a viewerof the detection zone 304 relative to the outer surface 237. The arrayof lenses or, lens array 311, includes one or more lenses 313.Correspondingly, a detection locus array 315 may be formed or identifiedon the second inner surface 239. The detection locus array 315 mayinclude one or more detection locus 317 backing surfaces. The lens array311 and detection locus array 315 may be arranged such that the centerof each lens 313 aligns with the center of a corresponding detectionlocus 317. Such alignment may be relative to a vector that isperpendicular to the viewing surface 233 or so that the focal points ofthe lenses are distributed along a common focal plane 319 (such that aplurality of axes extending from each the center of each detection locus317 and its corresponding lens 313 intersect at the focal plane 319). Inthis manner, the lenses may be operable to collect chemiluminescentlight emanating from the detection loci and to detect or image thecollected light along the focal plane, which may involve transmittingthe collected through one or more lenses of a mating adapter and onto aCMOS or comparable sensor of a computing device positioned within themating adapter.

In some embodiments, each of the first plate 215 and the second plate213 may be formed from a hydrophilic material, such as a clear,hydrophilic polymer. In other embodiments, the channel facing surfacesof the first plate 215 and/or second plate 213 may be coated with ahydrophilic coating. The outer surface 237 or second inner surface 239of the second plate 213 may also or alternatively be provided with orformed with a metalized coating or other reflective surface coating (orintegral reflective property) in order to reflect light back toward theviewer. In some embodiments, the second plate 213 may be made from areflective material. The coating may be applied broadly across the firstsurface or at the location one or more of the detection loci 317.Further, each detection locus 317 may correspond to an indentation,which may be a parabolic indentation, a frustoconical, a curvedindentation, or any other suitable type of indentation which, in anycase, may function to increase the amount of light that is able to becollected a viewed by a detector (e.g., a computing device).Correspondingly, each lens 313 may include curvature that also operatesto facilitate light collection and viewing (and corresponding analysisof photoluminescence of a hypothetical assay). In addition to themetalized coating described above, each detection locus 317 or the arrayof detection loci or (array of indentations) may also be prepopulatedwith a biological receptor. As referenced herein, a biological receptoris designed to bind with a certain analyte or biologic or chemicaltarget, which after further bio-chemical processing may result in thegeneration of a detectable biochemical response. Examples of biologicalreceptors include proteins, antibodies and oligonucleotides thatfacilitate the detection of a target pathogen or other target substance(such as a protein). An example of a biochemical response could bechemiluminescence generated by an ELISA assay format.

It is further noted that while only two plates are shown in FIG. 10, insome embodiments multiple sets of capillary plates may be layered uponeach other so that, for example, a first capillary channel having thefeatures described above would overlie a second (or third or fourth ornth) capillary channel also having the features described above. In suchan embodiment, the lenses or other focusing features on the variousplates may be configured to focus on a common focal plane, so that asingle sensor or sensor array may be able to simultaneously analyzesignals (e.g., light from one or more chemiluminescent processes). Suchan embodiment may provide for the multiplexing of signals or otherwiseenhance a device's ability to perform an assaying process using alimited amount of viewing area by allowing detection loci to be placedcloser to each other without liquids associated with the loci mixingtogether in an undesirable manner.

Referring now to the operational aspects of the specimen processingcartridge 100, upon a first actuation event (e.g., a user depressing theactuator 114), the sample collection liquid may be motivated from thefirst fluid source 121 and through the specimen receiving chamber 134 tostrip a biological sample from a collector (e.g., a swab) and to suspendthe sample in the first liquid, thereby acquiring the specimen in asuspension or solution. The process of actuating the actuator 114 mayprovide sufficient pressure to the sample collection liquid to cause thesample collection liquid to flow to the downstream reservoir. Theseprocesses may occur when the specimen processing cartridge 100 isoriented approximately as shown in FIG. 1, with the button or bulb thatforms the actuator 114 facing upward (relative to gravity) and thespecimen processing cartridge 100 being approximately upside-downrelative to the orientation depicted in FIG. 4.

The orientation of FIG. 4, and substantially similar orientations may beconsidered “wicking orientations” that permit liquid to flow out of thedownstream reservoir 130 through the wicking pad 138 via an upwardwicking action. As a result of the specimen processing cartridge 100having the described configuration and being in the opposing orientation(in which the sample collection liquid does not contact the wicking pad138), the sample collection liquid will first be retained in the portionof the downstream reservoir 130 that does not contact the wicking pad138. When the specimen processing cartridge 100 is flipped over towicking orientation (substantially as depicted in FIG. 4), the samplecollection liquid will contact the wicking pad 138 and begin to flow(via wicking action or a combination of wicking action and capillaryflow, as described in more detail below) toward the fluid sink 144. Thespecimen processing cartridge 100 can thereby be held in the non-wickingposition until the user is ready to commence additional processing, atwhich time the user may flip the specimen processing cartridge 100 tothe wicking orientation to begin processing.

Subsequently, contemporaneously, or previously, the user may insert thespecimen processing cartridge 100 into a mating adaptor 180 (see FIG. 7)or alternative external device that includes actuation posts that areconfigured to engage the similar device that include the first storagereservoir 122 and second storage reservoir 124 via the first actuationport 102 and second actuation port 104. The mating adaptor 180 mayinclude separate receiving areas for receiving the specimen processingcartridge 100 and a computing device 190, which may be a cell phone, andinclude the referenced actuation posts, and is configured such that acamera of the computing device aligns with the viewing area 140 of thespecimen processing cartridge 100 when both devices are inserted intothe mating adaptor. An example of such a configuration is described inpatent application Ser. No. 14/962,998, the subject matter of which isherein incorporated by reference.

Subsequent processes may be actuated by inserting the specimenprocessing cartridge 100 into the mating adaptor 180 and/or orientingthe assembled specimen processing cartridge 100, mating adaptor, andcomputing device so that the computing device is facing upward toward auser and the specimen delivery cartridge is in the wicking orientation.In the wicking orientation, the sample collection liquid in thedownstream reservoir 130 comes into contact with the first end of thewicking pad 138, which wicks the sample collection liquid upward towardviewing area 140 and fluid sink 144. Further, the liquids stored in thefirst storage reservoir 122 and second storage reservoir 124 are forcedby the actuation posts of the mating adaptor into the intermediatereservoir 126. These liquids, having been separated while being stored,are now permitted to mix when in the intermediate reservoir 126.

A intermediate reservoir outlet 136 is positioned similarly to thewicking pad 138, in that the (now) mixed liquid that has been forcedinto the intermediate reservoir 126 does not contact the dissolvablemembrane 150 positioned at the intermediate reservoir outlet 136 untilthe specimen processing cartridge 100 has been placed in the wickingorientation. In some embodiments, the liquid stored in the first storagereservoir 122 is luminol and the liquid stored in the second storagereservoir 124 is hydrogen peroxide that is operable to mix with theluminol. The mixed liquid may provide illumination at the testing areain the presence of a target pathogen-detecting antibody-capture antibodycomplex owing to the functionalization of the detection antibody with anenzyme, such as horseradish peroxidase (HRP). This may result in thegeneration of a chemiluminescent signal upon reaction with thepreviously described luminol-H₂O₂ mixture as the mixture progresses overthe detection zone (either due to wicking or capillary action).

As noted above, the dissolvable membrane 150 serves, in combination with(optional gasketing) at the intermediate reservoir outlet 136, to form afrangible, sealed interface between the intermediate reservoir 126 anddownstream reservoir 130. The dissolvable membrane 150 thereby occludesflow through the intermediate reservoir fluid outlet 136 when thedissolvable membrane 150 is in a first, undissolved state, and permitsflow from the intermediate reservoir 126 to the downstream reservoir 130when in a second, dissolved state.

The dissolvable membrane 150 may operate as a timing mechanism becausethe membrane material is selected to have a composition and thicknessthat is operable to dissolve after a desired, predetermined amount oftime after the membrane has been exposed to the liquid in the downstreamreservoir 130 (i.e., the mixed liquid referenced above). Moreover, theapplication of hydraulic force from the actuation posts may result inthe application of increased pressure at the intermediate reservoir 126,which may in turn result in the expansion of the expandable, elasticdiaphragm 128. The expansion of the expandable, elastic diaphragmoperates as a store of potential energy until the dissolvable membraneruptures, at which point elastomeric properties of the expandable,elastic diaphragm 128 cause the expandable, elastic diaphragm 128 toapply a hydraulic force that motivates the mixed liquid from theintermediate reservoir 126 to the downstream reservoir 130.

Prior to dissolution of the dissolvable membrane 150, however, thewicking properties of the wicking pad 138 facilitate conduction of thesample collection liquid (that now includes the suspended or dissolvedspecimen) across the viewing area 140 and excess liquid is absorbed atthe fluid sink 144. In some embodiments, dried reagents may bepre-deposited on (or affixed to) the portion of the wicking pad 138 thatunderlies the viewing area 140 (i.e., at the detection zone). Thosereagents may attract and/or interact with particles of the sample as thesample collection liquid flows across the wicking pad 138.

After a desired time delay, dissolution of the dissolvable membrane 150and hydraulic force provided by the expandable, elastic diaphragm 128result in the mixed liquid from the intermediate reservoir 126 flowingthrough the intermediate reservoir outlet 136 and into the downstreamreservoir 130. The mixed liquid may be a wash, and active solution(e.g., a luminol peroxide), a lysing agent, or a reagent suspension thatis operable to interact with particles from the specimen at the viewingarea 140. The mixed liquid may be formed by mixing (for example) aliquid from the first storage reservoir 122 with a liquid from thesecond storage reservoir 124. In addition, or in the alternative,additional fluid sources and corresponding actuation posts, secondaryreservoirs, and dissolvable membranes may be provided so that any numberof different liquids may be delivered in series or in parallel (asdetermined by the time delay corresponding to the applicable dissolvablemembrane(s)) to the downstream reservoir 130 and, correspondingly, thewicking pad 138. For the purposes of brevity, however, only a singlemixed liquid and a single intermediate reservoir are discussed.

In some embodiments, the mixed liquid is selected to be a wash, anactive solution that is operable to displace the sample collectionliquid, or an active solution operable interact with sample particles orreagent at the viewing area 140. If used, additional fluid may alsoinclude for example, a lysing agent or a reagent that may interact withtarget pathogens to cause a reaction that reveals the presence of thetarget.

In some embodiments, the mixed liquid, or a second or other liquid thatis subsequently delivered to the viewing area 140, may be a liquid thatfacilitates viewing of the test carried out at the viewing area 140,such as a luminol peroxide. In such embodiments, the luminol peroxidemay be used to interact with a portion of a specimen after initialprocessing to initiate a chemiluminescent reaction that may be observedto determine whether a target pathogen is present. In some embodiments,one or more pre-dried reagents are placed at predetermined locations onthe portion of the wicking pad 138 that underlies the viewing area. Thepre-dried reagents may be operable to react with one or more of thesample, the mixed fluid, or another fluid that wicks across the wickingpad 138.

Operation of the specimen processing cartridge 100 may further includeanalyzing the viewing area 140 after the sample collection liquid(including the specimen) has wicked across the viewing area 140 or at alater time when both of the sample collection liquid and the mixedliquid have wicked across the viewing area. The analysis may includeanalyzing one or more locations of the wicking pad 138 where the samplecollection liquid, mixed liquid, and (optionally) one or more subsequentliquids may have interacted with one another or with one or morepre-dried reagents positioned on the wicking pad 138 to determinewhether a target substance or pathogen was present in the specimen. Theforegoing method may be iterative and to that end, may involve anynumber of secondary liquids using the time-delay mechanisms describedabove to achieve an ordered and timed sequence of liquid interactions.For example, in some embodiments, a second fluid may be a wash fluid anda third fluid may include a reagent that interacts with portions of thewicking pad that are populated with a binding agent that capturesportions of the specimen from the sample collection liquid.

In some embodiments, each of the one or more fluid sources (e.g., firststorage reservoir 122, second storage reservoir 124, . . . . and nthstorage reservoir) be actuated simultaneously to deliver liquids to thewicking pad 138 in a timed sequence based on differences in time forwhich a respective dissolvable membrane ruptures in the presence of theapplicable liquid. The such embodiments, the fluid sources may deliverfluid to downstream reservoirs that are included by, for example,dissolvable membranes of different thicknesses. In such embodiments, thesample collection liquid may be delivered to the wicking pad 138 at afirst time, a second or mixed fluid may be delivered to the wicking pad138 at a second time that is later than the first time, a third fluidmay be delivered to the wicking pad 138 at a third time that is laterthan the second time, and so on.

In embodiments in which the wicking pad is coupled to a capillary plateapparatus, the wicking properties of the wicking pad 138 may conduct theliquids to the capillary plate apparatus (209), thereby dispersing thefirst liquid along with particles of the sample to detection locationsthat are deposited across portions of the backing surface of thedetection loci 317. In some embodiments, dried reagents may bepre-deposited on (or affixed to) the second plate 213 at the detectionzone 204 attract and/or interact with particles of the sample includedin the sample collection liquid flow across the capillary plateapparatus.

In any event, the mixed or another secondary liquid may be conductedacross the viewing area 140, and may be a wash, or an active solutionthat is operable to displace the first liquid and optionally to interactwith sample particles or reagent at the viewing area 140. The secondliquid may include, for example, a lysing agent or a reagent that mayinteract with target pathogens to cause a reaction that reveals thepresence of the target. The reaction sequence may be selected to suchthat the sample particles interact with reagents or receptors at theviewing area 140 to provide a visual indication of the presence orabsence of a target pathogen in the sample, which may be detectedvisually by a user or using the lens and camera functionality of acomputing device (e.g., a mobile device or smartphone).

It is noted that unless an embodiment is expressly stated as beingincompatible with other embodiments, the concepts and features describedwith respect to each embodiment may be applicable to and applied inconnection with concepts and features described in the other embodimentswithout departing from the scope of this disclosure. To that end, theabove-disclosed embodiments have been presented for purposes ofillustration and to enable one of ordinary skill in the art to practicethe disclosure, but the disclosure is not intended to be exhaustive orlimited to the forms disclosed. Many insubstantial modifications andvariations will be apparent to those of ordinary skill in the artwithout departing from the scope and spirit of the disclosure. The scopeof the claims is intended to broadly cover the disclosed embodiments andany such modification.

As used herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprise”and/or “comprising,” when used in this specification and/or the claims,specify the presence of stated features, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, steps, operations, elements, components, and/orgroups thereof. In addition, the steps and components described in theabove embodiments and figures are merely illustrative and do not implythat any particular step or component is a requirement of a claimedembodiment.

1. A lateral flow assaying apparatus comprising: a first plate having aviewing surface and an inner surface, the inner surface facing away fromthe viewing surface; a second plate, the second plate being offset fromthe first plate, wherein the second plate comprises a channel-facingsurface; a capillary channel formed by the inner surface of the firstplate and the channel-facing of the second plate, wherein the secondplate is offset from the first plate at a distance that facilitates flowby capillary action between the inner surface of the first plate and thechannel-facing surface of the second plate; and a detection zonecomprising at least one detection locus positioned within the capillarychannel.
 2. The lateral flow assaying apparatus of claim 1, wherein thedetection zone further comprises a lens integrated into the viewingsurface of the first plate and overlying the detection locus in thechannel-facing surface of the second plate, wherein the lens has a focalpoint that is offset from the viewing surface in the opposite directionof the inner surface.
 3. The lateral flow assaying apparatus of claim 1,wherein the detection locus comprises an indentation formed in a backingsurface of the second plate, the backing surface opposing thechannel-facing surface.
 4. The lateral flow assaying apparatus of claim3, wherein the at least one detection locus comprises a biologicalreceptor.
 5. The lateral flow assaying apparatus of claim 4, wherein thebiological receptor comprises an antibody.
 6. The lateral flow assayingapparatus of claim 4, wherein the biological receptor comprises anoligonucleotide.
 7. The lateral flow assaying apparatus of claim 1,wherein the at least one detection locus comprises an array of loci, andwherein each detection locus of the array is aligned with an indentationformed in a backing surface of the second plate, the backing surfaceopposing the channel-facing surface.
 8. The lateral flow assayingapparatus of claim 7, wherein the detection zone further comprises anarray of lenses integrated into the viewing surface of the first plateand overlying the array of indentations of the second plate, whereineach lens of the array of lenses has a focal point that is aligned witha common focal plane, the common focal plane being offset from theviewing surface in the opposite direction of the inner surface, andwherein each lens is aligned with a respective indentation of the arrayof indentations.
 9. The lateral flow assaying apparatus of claim,wherein backing surface of the second plate comprises a reflectivecoating.
 10. The lateral flow assaying apparatus of claim 1, wherein thesecond plate comprises a reflective material.
 11. The lateral flowassaying apparatus of claim 1, wherein at least a portion of the firstplate is transparent.
 12. The lateral flow assaying apparatus of claim1, wherein the first plate and second plate comprise a hydrophilicmaterial selected from the group consisting of a hydrophilic polymer,glass, and sapphire.
 13. The lateral flow assaying apparatus of claim 1,further comprising a wicking pad positioned between the first plate andthe second plate at a first end, the wicking pad being operable todeliver a liquid to the capillary channel.
 14. The lateral flow assayingapparatus of claim 1, further comprising a fluid sink coupled to asecond end of the lateral flow assaying apparatus, the fluid sinkcomprising a cellulose pad.
 15. A method for detecting a target using alateral flow assaying apparatus, the method comprising: delivering afirst liquid from a first fluid source to a capillary channel of thelateral flow assaying apparatus, the first liquid including a biologicalsample; analyzing at least one location of a detection zone; anddetermining whether the target is present based on a luminescence of theat least one location of the detection zone, wherein the lateral flowassaying apparatus comprises: (i) a first plate having a viewing surfaceand an inner surface, the inner surface facing away from the viewingsurface, (ii) a second plate, the second plate being offset from to thefirst plate, wherein the second plate comprises a channel-facing surfaceand an opposing backing surface, (iii) a capillary channel formed by theinner surface of the first plate and the channel-facing surface of thesecond plate, wherein the second plate is offset from the first plate bya distance that facilitates flow by capillary action between the innersurface of the first plate and the channel-facing surface of the secondplate, and (iv) a detection zone comprising at least one detection locuspositioned within the capillary channel.
 16. The method of claim 15,further comprising delivering a second liquid from a second fluid sourceto the capillary channel, the second liquid comprising luminol peroxide.17. A specimen processing cartridge having a lateral flow assayingapparatus comprising: a first plate having a viewing surface and aninner surface, the inner surface facing away from the viewing surface; asecond plate, the second plate being offset from the first plate,wherein the second plate comprises a channel-facing surface and anopposing backing surface; a capillary channel bounded by the innersurface of the first plate and the channel-facing surface of the secondplate; and a detection zone comprising at least one detection locuspositioned within the capillary channel.
 18. The specimen processingcartridge of claim 17, wherein the inner surface of the first platecomprises a first, hydrophilic surface and wherein the channel-facingsurface of the second plate comprises a second, hydrophilic surface,wherein the at least one detection locus comprises an array of detectionloci, each detection locus of the array comprising a biological receptorpositioned thereon, the lateral flow assaying apparatus furthercomprising, wherein the backing surface comprises a reflective surfaceoperable to reflect light toward the capillary channel, and wherein thefirst plate comprises a plurality of lenses, each lens corresponding toa detection locus.
 19. The specimen processing cartridge of claim 18,wherein the biological receptors comprise antibodies.
 20. The specimenprocessing cartridge of claim 18, wherein the reflecting surfacecomprises an array of reflectors, each reflector corresponding to adetection locus and comprising a metalized coating optimized to areflect a selected wavelength of light.